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TGF - β Signaling Pathway

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The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
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The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
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Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
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The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
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Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
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Despite the protective membrane that separates a cell from the environment, cells need the ability to detect and respond to environmental changes. Additionally, cells often need to communicate with one another. Unicellular and multicellular organisms use a variety of cell signaling mechanisms to communicate with the environment.
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Related Experiment Video

Updated: Jun 20, 2025

Stimulation of Notch Signaling in Mouse Osteoclast Precursors
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Signaling pathways associated with Lgr6 to regulate osteogenesis.

Justin S King1, Matthew Wan1, Yadav Wagley2

  • 1Department of Orthopaedic Surgery, The Musculoskeletal Research Institute, UCONN Health, Farmington, CT 06032, USA.

Bone
|July 21, 2024
PubMed
Summary

Leucine-rich repeat-containing G-protein coupled receptor 6 (Lgr6) is crucial for skeletal stem cell function and bone healing. This study reveals Lgr6

Keywords:
BmpBone regenerationPeriosteumSkeletal stem/progenitor cellsWnt

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Skeletal Phenotype Analysis of a Conditional Stat3 Deletion Mouse Model
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Area of Science:

  • Biochemistry
  • Cell Biology
  • Regenerative Medicine

Background:

  • Fracture healing relies on bone's natural repair mechanisms, with limited therapeutic options.
  • Targeting skeletal stem/progenitor cells (SSPCs) offers a promising therapeutic strategy for bone repair.
  • Understanding the molecular regulation of SSPCs is critical for developing new treatments.

Purpose of the Study:

  • To investigate the role of Leucine-rich repeat-containing G-protein coupled receptor 6 (Lgr6) in skeletal stem/progenitor cells (SSPCs) and osteogenesis.
  • To explore the molecular mechanisms by which Lgr6 influences bone healing and osteogenic differentiation.
  • To identify potential therapeutic targets for enhancing fracture healing.

Main Methods:

  • Utilized biochemical approaches and RNA sequencing to analyze gene expression.
  • Employed bioinformatic analysis of published single-cell data.
  • Investigated Lgr6 expression during bone morphogenetic protein (Bmp)-mediated osteogenesis in human and murine cells.

Main Results:

  • Identified Lgr6 expression in SSPC subpopulations, essential for bone volume maintenance and fracture healing.
  • Demonstrated that Lgr6 influences both canonical Wnt (cWnt)-independent and -dependent pathways.
  • Found that Bmp signaling elements, including pSMAD and gene ontology pathways, are downregulated in Lgr6-deficient cells.
  • Observed enhanced Lgr6 expression during Bmp-mediated osteogenesis.

Conclusions:

  • Uncovered a molecular interdependency between Bmp signaling and Lgr6 in osteogenesis.
  • Lgr6 plays a significant role in regulating SSPC behavior and bone regeneration.
  • These findings provide novel insights into osteogenesis and identify potential targets for improving fracture healing therapies.